title: The antitumor activity of zinc(II) and copper(II) complexes with 5,7-dihalo-substituted-8-quinolinoline.
abstract: [Zn₂(ClQ)₄(CH₃OH)₂] (1), [Zn(BrQ)₂(H₂O)₂] (2), [Zn₂(ClIQ)₄] (3) and [Cu(BrQ)₂] (4) (H-ClQ = 5,7-dichloro-8-hydroxylquinoline, H-BrQ = 5,7-dibromo-8-hydroxylquinoline, and H-ClIQ = 5-chloro-7-iodo-8-hydroxylquinoline) were synthesized. Compounds 1-4 showed high anti-proliferative cytotoxicities against BEL-7404, SK-OV-3, NCI-H460 tumor cells, and HL-7702 normal cells in vitro, with IC₅₀ values in the 1.4 nM to 32.13 μM range. Compounds 2-4 exhibited significantly enhanced cytotoxicity against BEL-7404 cell line, comparing with free 5,7-dihalo-8-quinolinol. Western blotting analysis showed that 2, 3 depleted mutant p53 protein in MDA-MB-231, and compound 2 decreased the ratio of Bcl-2/Bax in NCI-H460 significantly. The binding abilities of 1-4 to DNA were stronger than that of free quinolinol ligand. Intercalation is the probable binding mode for the complexes and free quinolinol ligands with DNA.
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Liu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wei
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Yun-Qiong
authors.initials: YQ
authors.lastname: Gu
authors.forename: Ke-Bin
authors.initials: KB
authors.lastname: Huang
authors.forename: Zhu-Quan
authors.initials: ZQ
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011804:Quinolines; D016159:Tumor Suppressor Protein p53; D003300:Copper
keywords: 5,7-Dihalo-substituted-8-quinolinoline; Crystal structure; Cu(II) complex; Cytotoxicity; DNA binding; Zn(II) complex